Researchers from the University of Washington have found that irinotecan-based therapy, a topoisomerase 1 inhibitor, can improve survival rates in a subset of patients with stage III colon cancer.
In the study, entitled “CpG Island Methylator Phenotype Is Associated With Response to Adjuvant Irinotecan-Based Therapy for Stage III Colon Cancer,” and published in the Gastroenterology journal, the team analyzed data from patients with stage III colon cancer randomly assigned to groups given either fluorouracil and leucovorin or adjuvant irinotecan after surgery, from April 1999 through April 2001 and followed for eight years. The primary and secondary endpoint of this trial was set to overall survival and disease-free survival, respectively.
Patients with tumors positive for CpG island methylator phenotype (CIMP), a subset of colorectal cancers featuring hypermethylation of multiple promoter CpG islands and accounting for 10% to 20% of colorectal cancers, showed increased overall survival if treated with irinotecan (69%) when compared to standard fluorouracil and leucovorin treatment (56%).
The results were more striking in patients who had stage III CIMP-positive, mismatch repair intact (MMR-I) colon cancer, a distinct subtype of colorectal cancer, comprising 12% to 17% of patient cases overall and presenting specific clinicopathologic features associated with a better prognosis.
Moreover, upon combining fluorouracil and leucovorin with adjuvant irinotecan therapy, patients with CIMP-positive tumors had improved overall survival rates. However, adding irinotecan in the treatment of patients with CIMP-negative tumors significantly decreased overall survival (68%) when compared to standard chemotherapy treatment (78%).
Importantly, the authors did not see any link between CIMP and KRAS or BRAF mutations, suggesting irinotecan treatment is not influenced by KRAS/BRAF mutation status.
“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer. Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting,” lead study author Stacey Shiovitz, MD, from the department of medicine, University of Washington, Seattle, WA, and the clinical research division of Fred Hutchinson Cancer Research Center, Seattle said in an American Gastroenterological Association press release.
Even though more studies are necessary to understand the mechanisms underlying the CIMP phenotype and larger subsets of patients are essential to further test these findings, Dr. Shiovitz highlighted “this analysis serves to increase our understanding of which subset of patients might benefit from irinotecan adjuvant therapy. This research is an important step in the medical community’s work to classify tumors into groups that would result in optimized treatment strategies, thus delivering a higher level of personalized care to patients”.
